There is evidence for the role of opioids in brain function and pituitary regulation. We propose to study the interrelationship between the catecholaminergic and opioid systems in women, and to investigate the developmental regulation of opioids, specifically, the enkephalins, in the ovine fetus. The administration of naloxone, a specific opiate antagonist, has facilitated evaluation of endogenous opioid function. Indeed, several investigators have recently shown that naloxone administration induces luteinizing hormone (LH) release in women. This naloxone induced LH release is consistent with the view that stimulation of opiate receptors inhibits LHRH secretion. There is increasing support for catecholaminergic mediation of these opioid effects on LH secretion. To test this hypothesis is hyperprolactinemic women, we propose to study the effect of a dopamine agonist on the release of LH and prolactin (PRL) induced by naloxone. This concept will be further evaluated by the administration of Alpha-adrenergic and dopaminergic blockers to normal women prior to naloxone infusion. Finally, the role of ovarian steroid feedback action on opioid modulation of gonadotropin and PRL secretion will be studied in post-menopausal women. During opiate stimulation or naloxone treatment, the pulsatile response of LH and PRL will be determined following varied steroid treatments. These studies should provide considerable evidence for a catecholaminergic role as a 'inter-neuronal connector' between the opioids and the LHRH neurons. In a separate series of studies performed in the ovine fetus, a technique for the measurement of methionine enkephalin (met-enk) in fetal cerebrospinal fluid (CSF) will be developed. If successful, this preparation will be used for chronic fetal CSF collection in utero. The transport of a met-enk analog, metkephamid, across the placental and fetal blood-brain barrier will be determined. In addition, the fetus will be administered naloxone or metkephamid centrally and peripherally. These series of experiments will assess the effect of these agents on fetal activity and behavior. Thus, these studies will be indicative of developmental changes in met-enk neurons and opioid function in utero.